Journal
MOLECULAR CELL
Volume 50, Issue 6, Pages 894-907Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2013.06.002
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Funding
- NIH Office of Research Infrastructure Programs [P40 OD010440]
- Leukemia and Lymphoma Society [3260-07]
- Arnold and Mabel Beckman Foundation
- NIH Director's New Innovator Award [1 DP2 OD006412-01]
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m The inhibition of transcriptional elongation plays an important role in gene regulation in metazoans, including C. elegans. Here, we combine genomic and biochemical approaches to dissect a role of ZFP-1, the C. elegans AF10 homolog, in transcriptional control. We show that ZFP-1 and its interacting partner DOT-1.1 have a global role in negatively modulating the level of polymerase II (Pol II) transcription on essential widely expressed genes. Moreover, the ZFP-1/DOT-1.1 complex contributes to progressive Pol II pausing on essential genes during development and to rapid Pol II pausing during stress response. The slowing down of Pol II transcription by ZFP-1/DOT-1.1 is associated with an increase in H3K79 methylation and a decrease in H2B monoubiquitination, which promotes transcription. We propose a model wherein the recruitment of ZFP-1/DOT-1.1 and deposition of H3K79 methylation at highly expressed genes initiates a negative feedback mechanism for the modulation of their expression.
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